Definition, evaluation, and management of treatment refractory mania

Treatment refractory mania is a common clinical problem. Unfortunately, the treatment of acute mania refractory to standard antimanic and mood-stabilizing medications has not been well studied. This review will discuss the definition, evaluation, and differential diagnosis of treatment refractory mania; the definition of an adequate treatment trial for acute mania; the identification of predictors of treatment response; and clinical trials in treatment refractory mania. Computerized searches of the medical literature regarding treatment refractory mania were undertaken using Paperchase (1966-2001), and bibliographies of all articles identified were reviewed to identify all relevant case reports, case series, clinical trials, and methodologic and phenomenologic reports. Operational definitions of treatment refractory mania were proposed based on sequential nonresponse to adequate trials of antimanic agents. The average time of onset of antimanic agents studied in randomized trials was 1 to 2 weeks. Clinical tools for assessing treatment response retrospectively and prospectively appear to have an important role in managing medication treatment in patients with bipolar disorder. Relatively few reliable predictors of treatment response to established antimanic agents have been identified. However, these predictors represent important factors in treatment selection to minimize the probability of nonresponse. Very few randomized, controlled trials of antimanic agents have been conducted in patients with treatment refractory mania. Field testing of treatment algorithms and systematic collection of data from naturalistic treatment studies should provide much-needed data regarding the efficacy of antimanic agents in treatment refractory mania.